The HNRC was established to provide scientific leadership and state-of-the-art resources for fostering innovative multidisciplinary neuroAIDS research. Indicators of success in this endeavor include the number and breadth of extramurally funded research studies and scientific publications supported by the HNRC, whose contributions have ranged from demonstrating the role of neurotrophic factors and gene dysregulation in neuroAIDS, to recognizing a potentially new form of leukoencephalopathy, to identifying the emerging role of hepatitis C infection and drugs such as methamphetamine in relation to neuroAIDS, to establishing innovative approaches for gauging the real-life consequences of HIV neurocognitive impairment (NCI). Moreover, the HNRC provided training, mentoring, and developmental grant opportunities to equip tomorrow's scientists with the capacity for breakthrough research. For this renewal, the HNRC focuses on five major neuroAIDS themes: (1) delineating the attributes of the virus, host, and host-virus interaction that determine HIV NCI;(2) identifying mechanisms by which host-virus factors generate neural injury and NCI;(3) understanding the role of co-pathogens and comorbidities;(4) developing strategies for optimizing treatment to prevent or ameliorate neuroAIDS;and (5) determining the real-life significance of NCI and its treatment. The HNRC is designed to respond proactively and flexibly to the changing terrain of neuroAIDS. Examples of the major resources include the expertise of investigators and staff, well-developed and practiced investigative procedures, an extensive and flexible database, a large longitudinal cohort, and an accessible fluid and tissue bank. Anticipating neuroAIDS priorities, the HNRC proposes to restructure and merge existing cores and establish two new cores: International and Neurovirology. International data can shed light on the contribution of host-virus factors to neuroAIDS. The International Core will facilitate development of HNRC activities in countries such as China, Brazil, and India. The Neurovirology Core builds expertise on the genetic and molecular bases of viral compartmentalization, neurovirulence, and divergence in ARV resistance, and will support studies on clade and host-virus genetics in other countries. The new structure of the HNRC thus includes cores in Neuromedicine. Neurobehavior, Neuroimaginq. Neuroviroloqy. and Neurobiology, as well as Developmental and International Cores. The efforts of these cores are harmonized through a Coordinating Core that includes Administrative, Data Management and Information Systems. Statistics, and Participant Accrual and Retention units. With these revised aims, processes, and structures, the HNRC envisions developing into an International Center of Excellence in neuroAIDS research and training.